Sutent

sunitinib malate

Sutent

Pharmacologic class: Receptor tyrosine kinase inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Hepatotoxicity, which has been observed in clinical trials and postmarketing experience, may be severe, and deaths have occurred.

Action

Inhibits multiple receptor tyrosine kinases, some of which are implicated in tumor growth, pathologic angio-genesis, and metastatic cancer progression

Availability

Capsules: 12.5 mg, 25 mg, 50 mg

Indications and dosages

GI stromal tumor after disease progression with or intolerance to imatinib mesylate; advanced renal cell carcinoma

Adults: 50 mg P.O. daily on cycle of 4 weeks on and 2 weeks off treatment; may increase or decrease dosage in 12.5-mg increments based on safety and tolerance

Dosage adjustment

• Concurrent use of strong CYP3A4 inducers or inhibitors

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:
• left ventricular dysfunction, hypertension, history of prolonged QT interval, concurrent use of antiarrhythmics, patients with relevant preexisting cardiac disease, bradycardia, or electrolyte disturbances
• patients who have experienced cardiac events within previous 12 months
• hepatotoxicity
• concurrent use of strong CYP3A4 inhibitors
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

Monitor liver function tests before start of treatment.
• Administer with or without food.
• Interrupt therapy or reduce dosage, as prescribed, in patients who lack clinical evidence of heart failure but have ejection fractions (EFs) below 50% and above 20% below baseline.

Adverse reactions

CNS: headache, asthenia

CV: hypertension, left ventricular dysfunction

EENT: epistaxis, oral pain

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, mucositis, stomatitis, anorexia

Hematologic: bleeding, anemia, thrombocytopenia, neutropenia, lymphopenia, hemorrhage

Hepatic: hepatotoxicity

Metabolic: acquired hypothyroidism, adrenal toxicity

Musculoskeletal: arthralgia, back pain, limb pain, myalgia

Respiratory: dyspnea, cough, pulmonary embolism

Skin: skin abnormalities, skin discoloration, rash, palmar-plantar erythrodysesthesia, alopecia, hair color changes

Other: altered taste, fatigue, fever

Interactions

Drug-drug.Atazanavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole: increased sunitinib blood level

Carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin: decreased sunitinib blood level

Drug-diagnostic tests.Amylase, creatinine, lipase, uric acid: increased

Liver function tests: abnormal

Serum phosphorus, potassium, sodium: decreased

Drug-food.Grapefruit juice, pomegranate: increased sunitinib blood level

Drug-herbs.Alpha-lipoic acid: decreased chemotherapeutic efficacy

American elder, bishop's weed, cat's claw, devil's claw, eucalyptus, feverfew, Siberian ginseng, valerian: increased sunitinib blood level

St. John's wort: unpredictable decrease in sunitinib blood level

Patient monitoring

• Obtain CBC with platelet count and blood chemistries (including phosphate) at start of each treatment cycle and frequently thereafter.
• Know that physician may order baseline and periodic evaluation of left ventricular EF in patients who experienced cardiac events within 12 months before starting drug. Watch closely for signs and symptoms of left ventricular dysfunction (especially heart failure).
• Be aware that physician may order baseline EF testing for patients without cardiac risk factors.
• Monitor for hypertension; administer standard antihypertensive therapy as ordered and needed.
• Monitor for adrenal insufficiency if patient experiences stress (as from surgery, trauma, or severe infection).

Monitor liver function tests during each cycle of treatment and as clinically indicated. Interrupt therapy for Grade 3 or 4 drug-related hepatic adverse events; discontinue drug if no resolution. Don't restart drug if severe changes in liver function tests subsequently occur or if patient has other signs and symptoms of liver failure.

Patient teaching

• Instruct patient to take drug with or without food.

Urge patient to immediately report sudden signs and symptoms of liver problems (such as yellowing of skin or eyes, unusual tiredness, loss of appetite), chest pain, swelling, or difficulty breathing.
• Tell patient drug may cause skin changes (drying, cracking, or rashes on hands or feet) and hair color changes.
• Advise patient to consult prescriber before taking other drugs, including over-the-counter drugs and herbs.
• Caution patient not to take St. John's wort during therapy.
• Advise female with childbearing potential to avoid pregnancy and breastfeeding during therapy.

•As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

SUNItinib

(su-ni-ti-nib) ,

Sutent

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Gastrointestinal stromal tumor (GIST) that has progressed or intolerance to imatinib.Advanced renal cell carcinoma (RCC).Advanced pancreatic neuroendocrine tumors (pNET).

Action

Inhibits multiple receptor tyrosine kinases, which are enzymes implicated in tumor growth, abnormal vascular growth, and tumor metastases.

Therapeutic effects

Decreased tumor spread.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: Sunitinib—95%; primary active metabolite—90%.
Metabolism and Excretion: Metabolized by the CYP3A4 enzyme system to its primary active metabolite. This metabolite is further metabolized by CYP3A4. Excretion is primarily fecal.
Half-life: Sunitinib—40–60 hr; primary active metabolite—80–110 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown6–12 hr24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy, lactation;Concurrent use of ketoconazole or St. John's wort.
Use Cautiously in: Hepatic/renal impairment;Concurrent use of bisphosphonates or a history of dental disease (may ↑ risk of jaw osteonecrosis) Obstetric: Childbearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • Reversible Posterior Leukoencephalopathy Syndrome (life-threatening)
  • fatigue (most frequent)
  • dizziness
  • headache

Cardiovascular

  • chf (life-threatening)
  • hypertension (most frequent)
  • peripheral edema
  • QT interval prolongation
  • thromboembolic events

Ear, Eye, Nose, Throat

  • epistaxis (most frequent)

Gastrointestinal

  • hepatotoxicity
  • diarrhea (most frequent)
  • dyspepsia (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • altered taste
  • anorexia
  • cholecystitis
  • constipation
  • esophagitis
  • ↑ lipase/amylase
  • ↑ liver enzymes
  • oral pain

Dermatologic

  • erythema multiforme (life-threatening)
  • alopecia
  • hand-foot syndrome
  • hair color change
  • impaired wound healing
  • rash
  • skin discoloration

Endocrinologic

  • hypothyroidism (most frequent)
  • adrenal insufficiency
  • hyperthyroidism

Fluid and Electrolyte

  • dehydration
  • hypophosphatemia

Hematologic

  • hemorrhage
  • anemia (most frequent)
  • lymphopenia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Metabolic

  • hyperuricemia (most frequent)

Musculoskeletal

  • arthralgia
  • back pain
  • limb pain
  • myalgia
  • osteonecrosis (primarily of jaw)

Miscellaneous

  • tumor lysis syndrome (life-threatening)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Ketoconazole and other inhibitors of the CYP3A4 enzyme system may ↑ levels and the risk of toxicity; ↓ dose to 37.5 mg daily (for GIST and RCC) or 25 mg daily (for pNET); avoid these strong inhibitors, if possible.Rifampin and other inducers of the CYP3A4 enzyme system may ↓ levels and effectiveness; ↑ dose to 87.5 mg daily (for GIST and RCC) or 62.5 mg daily (for pNET); avoid these strong inducers, if possible.Concurrent use with alendronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, or zoledronic acid may ↑ risk of jaw osteonecrosis↑ risk of microangiopathic hemolytic anemia when used with bevacizumab (concurrent use not recommended).St. John's wort may ↓ levels and effectiveness; avoid concurrent use.Blood levels and effects are ↑ by grapefruit juice; concurrent use should be avoided.

Route/Dosage

GIST and RCC

Oral (Adults) 50 mg once daily for 4 wk, followed by 2-wk rest; alteration of dose is based on safety/tolerability and is made in 12.5-mg increments/decrements.

pNET

Oral (Adults) 37.5 mg once daily.

Availability

Capsules: 12.5 mg, 25 mg, 37.5 mg, 50 mg

Nursing implications

Nursing assessment

  • Monitor for signs of HF (dyspnea, edema, jugular venous distention) during therapy. Assess left ventricular ejection fraction (LVEF) at baseline and periodically during therapy in patients with cardiac events in the previous 12 mo and a baseline ejection fraction in patients without cardiovascular risk factors. Discontinue sunitinib if signs of HF occur.
  • Monitor for hypertension and treat with standard antihypertensive therapy. If severe hypertension occurs, may discontinue sunitinib until controlled.
  • Monitor ECG and electrolytes periodically during therapy; may cause QT prolongation and torsades de pointes.
  • Lab Test Considerations: Monitor CBC with platelet count and serum chemistries including phosphate at the beginning of each treatment cycle. May cause neutropenia, lymphopenia, anemia, and thrombocytopenia. May cause ↑ creatinine, hypokalemia, hyperuricemia, and ↑ uric acid.
    • Monitor ALT, AST, and bilirubin before starting therapy, during each cycle of treatment, and as clinically indicated. Stop therapy if Grade 3 or 4 drug-related hepatic adverse events occur and discontinue if there is no resolution. Do not restart sunitinib if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure. May cause ↑ AST, ALT, alkaline phosphatase, total and indirect bilirubin, amylase, and lipase.
    • Monitor thyroid function at baseline and in patients with symptoms of hypothyroidism or hyperthyroidism. May be treated with standard medical practice.

Potential Nursing Diagnoses

Diarrhea (Adverse Reactions)
Nausea (Adverse Reactions)

Implementation

  • Do not confuse sunitinib with sorafenib.
  • Oral: Administer once daily with or without food.

Patient/Family Teaching

  • Instruct patient to take sunitinib as directed. Take missed doses as soon as remembered, but not just before next dose. Take next dose at regular time. Do not take more than 1 dose at a time. Tell your health care professional about the missed dose.
  • Advise patient to avoid grapefruit juice and grapefruit products during therapy.
  • Instruct patient to notify health care professional promptly if signs of liver failure (itching, yellow eyes or skin, dark urine, pain or discomfort in the right upper stomach area) or tumor lysis syndrome (nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness) occur.
  • Advise patient that GI disorders (diarrhea, nausea, stomatitis, dyspepsia, vomiting) are common and may require antiemetic and antidiarrheal medications.
  • Inform patient that sunitinib may cause discoloration (yellow) of skin and depigmentation of hair or skin.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise patient to notify health care professional if bleeding or swelling occur.
  • Advise women of childbearing potential to avoid becoming pregnant while receiving sunitinib.

Evaluation/Desired Outcomes

  • Decrease in tumor spread.

Sutent

a trademark for sunitinib.
References in periodicals archive ?
Contract award: drug delivery - esbriet - l04ax05, sutent - l01xe04.
Sutent (sunitinib), oral capsule for the treatment of three types of cancer: advanced renal cell carcinoma, gastrointestinal stromal tumors after disease progression or intolerance to prior therapy, and pancreatic neuroendocrine tumors.
Ade was diagnosed with the disease in 2007, just two weeks after the couple's honeymoon, and was given just a year to live, but enjoyed another three thanks to the life-extending drug Sutent.
Paul Higham, CEO of immatics, said: "We are extremely pleased that Pfizer has committed to supporting our pivotal Phase III trial with IMA901 with the supply of Sutent.
It follows a similar drug, Sutent, being made available on the NHS in 2009 following a lengthy battle to make it more accessible to patients.
Sutent is already approved as a treatment for kidney cancer and for tumors of the stomach, esophagus, and bowels that do not respond to other treatment.
said that it stopped a late-stage clinical study of its drug Sutent as a treatment for liver cancer.
Health Minister Edwina Hart decided in January that all patients with kidney cancer should have access to the three drugs and another, Sutent, in the absence of final Nice guidance.
Kidney cancer patients around the UK have won their campaign for access to sunitinib, marketed as Sutent, on the NHS.
CLINICIANS and senior managers involved in cancer care in the North East have welcomed the National Institute for Clinical Excellence's decision to approve Sutent for first line treatment of advanced kidney cancer.
The National Institute for Health and Clinical Excellence (Nice) published revised guidance on Sutent (sunitinib).
The breakthrough will see all Local Health Boards (LHBs) in Wales ordered to fund Sutent, Nexavar, Avastin and Torisel - even though they have not been formally approved for NHS use.